Table 2.

Exome-Variant Filtration Steps and Results of the Pedigree

Filtration Steps	SNVs	indels
Step 1): QC passed variants a	384102	45898
Step 2): novel variants b	204610	33009
Step 3): Protein-altering c or splice region variants	1589	478
Step 4): Variants segregated with disease d	14	3
Step 5): Variants predicted to be deleterious e	11	3
Candidate variants list	11	3
Step 6): familial segregation analysis f	4	2
Step 7): absent from the second-generation unaffected members	1	0
The final etiologic variant	NFX1 c.2519T>C

^aSNVs and indel variants filtered by variant quality score recalibration (VQSR) measurement using GATK’s recommended parameters;

^bNovel variants, absent from public databases (ExAC_EAS);

^cNonsynonymous, stop-gain, frameshift, start-lost, stop-lost;

^dVariants present in the three affected individuals (II-2, II-4, III-1) and absent in the phenotypically normal participants (II-5, III-4) sent for ES;

^eVariants predicted to be deleterious with CADD≥10 or truncating variants;

^fVariants segregated fully with definite IA phenotype in the family.